An N-6-methyladenosine-associated lncRNA signature for predicting clinical outcome and therapeutic responses in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the leading cause of tumor-related mortality worldwide. N-6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) have been reported to play significant roles in prognosis assessment and decision-making strategies for HCC. This study aimed to investigate the significance of prognosis and treatment response assessment of m6A-related lncRNAs in HCC. Methods: We used Pearson's correlation coefficient (r) to identify m6A-associated lncRNAs. We then performed univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses on the screened m6A-related lncRNAs to build a prognostic risk model for patients with HCC. The prognostic values and predictive performance of the model were then analyzed through KaplanMeier curve, receiver operating characteristic (ROC) curve, and nomogram. In addition, the potential value of this model for assessing sorafenib or immunotherapeutic responses was investigated based on the R package "pRRophetic" and immunophenoscore (IPS), respectively. Results: Fourteen m6A-related lncRNAs were identified to construct the predictive model (P<0.05). Patients with high risk showed poorer survival than those with low risk. The risk score may serve as an independent predictor for the prognosis of patients with HCC even in the subgroup analysis. Moreover, our predictive model outperformed TP53 mutation status or tumor mutation burden (TMB) scores in the stratification of patient survival. Notably, high- and low-risk patients were shown to have different estimated responses for sorafenib and immunotherapies. Conclusions: This study identified that a novel 14-m6A-related lncRNA signature could be a promising predictor for patient survival, and it might provide a vista for treatment response assessment of chemotherapy and immunotherapy.